The present invention relates to a probe for use in an xe2x80x9cintermolecular force microscopexe2x80x9d which analyzes/processes a surface of a solid substance by utilizing a chemical reaction, and a production method of such a probe. The present invention further relates to a scanning probe microscope incorporating such a probe, and a molecule processing method using such a scanning probe microscope.
A measurement apparatus called a xe2x80x9cscanning probe microscopexe2x80x9d examines information over a surface of a solid substance by scanning a predetermined range of the surface of the solid substance with a sharp-tip probe placed in the close vicinity of the surface of the solid substance at the accuracy of angstroms, and measuring an interaction caused between the probe and the surface of the solid substance during the scanning operation. There are various scanning probe microscope proposed in accordance with the type of interaction to be measured. For example, when the interaction is a tunneling current, a scanning tunneling microscope is employed; when the interaction is interatomic force, an atomic force microscope is employed; and when the interaction is magnetic force, a magnetic force microscope is employed.
There are proposed xe2x80x9cintermolecular force microscopesxe2x80x9d, where a molecule having a chemical sensor function, or a molecule of a catalyst, is fixed at the tip of a probe of a scanning probe microscope, and a chemical interaction or catalysis caused between the molecule at the tip of the probe and the molecule to be measured is utilized to examine or process chemical information of the molecule to be measured (Japanese Patent No. 2653597; Japanese Patent No. 2561396; Nakagawa, xe2x80x9cShokubai (catalyst)xe2x80x9d, Vol 39, pp. 628-635, 1997). The principle of an intermolecular force microscope composed by fixing a sensor molecule to a probe of an atomic force microscope is described below. Herein, a xe2x80x9cchemical sensor functionxe2x80x9d refers to a function of analyzing a chemical characteristic of an organic molecule. In general, a chemical characteristic of a molecule is determined by the three-dimensional structure of the molecule or a functional group included in the molecule. A sensor molecule having a chemical sensor function can specifically examine such a structure or functional group.
FIG. 11 illustrates the principle of an atomic force microscope. A sample 153 is fixed on a piezoelectric element 154 extendable in X-, Y-, and Z-directions. A probe 114, which includes a tip having the radius of curvature of several tens of nanometers, is present above the sample 153. The probe 114 is fixed at the tip of a lever portion 152. When force is applied between the sample 153 and the probe 114, the lever portion 152 is deflected. This deflection can be evaluated by measuring with two photodiodes 155 the variation in the reflection angle of a laser beam 151 reflected by the lever portion 152. Therefore, force caused between the sample and the probe can be calculated from the product of the amount of deflection and the spring constant of the lever portion. Thus, force caused between the sample and the probe is measured while scanning a specific region of the sample on an X-Y plane with the piezoelectric element, whereby information on the surface of the sample can be examined.
For example, an X-Y region is scanned while applying feedback to the movement of the piezoelectric element in the Z-direction such that force caused between the sample and the probe is maintained to be constant, whereby the relationship of the movement of the piezoelectric element in the X-, Y-, and Z-directions is examined. Through such an examination, concaves/convexes of the sample can be evaluated. Herein, a sensor molecule is fixed to the tip of the probe for measuring a surface of a base material on which other types of molecules are present, so that the position of a specific molecule can be examined. That is, in the case where the sensor molecule is a molecule that causes strong attractive force only with a molecule (molecule A), the position of molecule A can be examined at a resolution of a molecular level by measuring the surface of the base substance on which the other types of molecules are present, with a probe having such a sensor molecule. Further, if a catalyst molecule is fixed to the probe, a specific molecule can be processed with such a probe.
A base sequence of a DNA can also be determined by using an intermolecular force microscope. In the case where adenine, which constitutes a DNA, is fixed to a probe, and a single stranded DNA fixed on the base material is measured, the position of thymine can be specified because adenine causes large attractive force with thymine in a DNA. The base sequence in the DNA can be examined by conducting a measurement in a similar manner using probes having thymine, guanine, and cytosine attached thereto.
In a conventional intermolecular microscope, a molecule is fixed to a probe such that the molecule covers an entire surface of the probe. Thus, without correct control of the distance between the probe and a sample, a large number of molecules on the probe come into contact with the molecule to be examined during an examination process, so that the measurement resolution is poor. Similarly, also in molecular processing using an intermolecular force microscope, it is difficult to process only a single molecule because a large number of molecules fixed on the probe cause interaction with the large number of molecules to be processed. Hereinafter, problems involved in conventional intermolecular force microscope are described in detail.
FIG. 12 diagrammatically illustrates an example where the position of molecule A 163, which is fixed on a surface of a solid substance, is examined using an intermolecular force microscope. When a probe is pressed against the surface of the solid substance, the surface of the solid substance is elastically deformed, so that two neighboring molecules, molecule A 163 and molecule B 164, cause an interaction, and as a result, the positions of these two molecules cannot be identified.
FIG. 13 is a conceptual diagram which illustrates an example of determining the position of adenine 174, which is a base included in a single stranded DNA 173, by using an intermolecular force microscope. Thymine 172, which causes a specific interaction with adenine, is fixed to a probe 171. In principle, the position of adenine 174 in a DNA can be examined by examining the position of adenine which causes an interaction with thymine 172 on the probe. However, if the probe 171 is too close to the sample, two or more thymine molecules 172 are specifically interacted with two or more adenine molecules 174 of the DNA strand 173. As a result, it becomes difficult to identify the position of adenine in the DNA strand 173.
FIG. 14 illustrates an example where a protein thin film fixed onto a base material is processed using an intermolecular force microscope. Peptidases, which are enzymes for decomposing a protein, are fixed to a probe 181. In this case, if force caused between the probe and a sample is too large, a large number of peptidases come into contact with the protein thin film. As a result, it becomes difficult to process the protein to a precision of a single molecule size.
It is readily appreciated that the above problems can be solved by fixing a sensor molecule or a catalyst onto a probe having the radius of curvature of angstroms. A proposed candidate for a probe having the smallest radius of curvature is a carbon nanotube. In recent years, there has been proposed a method for fixing a carbon nanotube to a probe of an AFM (atomic force microscope) and fixing an organic molecule to the carbon nanotube (D. Hongjie, et al., Nature; vol. 384, p.147, 1996). However, even a carbon nanotube has a radius of curvature of 2.6 nm at the tip thereof, and accordingly, the number of molecules formed in the region (tip surface) at the tip of the probe which faces a sample is about several hundreds. Thus, similarly as described above, a large number of molecules on a probe causes interactions with molecules of a sample without providing strict control of force between the probe and the sample.
The present invention relates to a probe for a scanning probe microscope. This probe includes: a proximal end; and a distal tip portion, wherein the distal tip portion has a tip surface which faces a fixed sample, and at least one monolayer is formed at least on the tip surface, and a molecule having a chemical sensor function or catalytic function is placed in or on an outermost monolayer above the tip surface.
Preferably, stacked monolayers are formed over the tip surface; and the molecular density in respective layers of the stacked monolayers decreasingly varies from the tip surface to the outermost layer.
Preferably, the at least one monolayer is formed by use of a covalent bond.
Preferably, the at least one monolayer is formed of an organic molecule; and the number of molecules included in an outermost monolayer above the tip surface is equal to or smaller than 100.
Preferably, the probe of the present invention includes stacked monolayers; a plurality of molecules having a chemical sensor function or catalytic function are provided in different monolayers; and the plurality of molecules have different chemical sensor functions or catalytic functions.
According to one aspect of the present invention, the present invention relates to a probe for a scanning probe microscope, which includes: a cover layer containing an electrically conductive polymer; and a catalyst in the cover layer, the catalyst being selected from a group consisting of inorganic catalysts and organic catalysts.
Preferably, a probe of the present invention further includes at least one organic molecular film formed on the cover layer, wherein a molecule having a chemical sensor function or catalytic function is placed in or on an outermost organic molecular layer.
Preferably, a function of the catalyst contained in the cover layer is different from a function of the molecule having the chemical sensor function or catalytic function.
According to one aspect of the present invention, the present invention relates to a method for producing the probe for a scanning probe microscope. This method includes steps of: (a) forming a monolayer on a probe; and (b) forming another monolayer on the monolayer, or modifying a molecular structure of a molecule included in the monolayer.
Preferably, the step (b) includes: substituting a molecule end of a molecule included in the monolayer with a functional group by means of a chemical reaction performed at a substitution efficiency of smaller than 1; and bonding the functional group to a molecule which is capable of being bonded to the functional group.
Preferably, the monolayer is formed of an organic molecule; and the step (b) includes bringing the distal tip portion of the probe into contact with a surface of a solid substance having a catalytic function, so that only the organic molecule at a tip surface of the distal tip portion of the probe is reactively modified.
Preferably, the monolayer is formed of an organic molecule: and the step (b) includes scanning with the probe a surface of a solid substance including at least one region which has a catalytic function, and reactively modifying only the organic molecule at the tip surface of the distal tip portion of the probe.
Preferably, the monolayer is formed of an organic molecule; when the organic molecule comes into contact with a solid catalyst in the presence of a substrate, a molecular structure of the organic molecule is modified by a chemical reaction; and the step (b) includes repeating reciprocation of the probe by moving the probe toward, and away from, a surface of the solid catalyst in the absence of the substrate, thereby adjusting an approach distance between the probe and the solid catalyst, and thereafter positioning the probe and the solid catalyst with the approach distance therebetween in the presence of the substrate, thereby modifying a molecular structure of the organic molecule.
Preferably, the above method may further include a step of bonding an organic molecule having a chemical sensor function or catalytic function to the modified organic molecule.
According to one aspect of the present invention, the present invention relates to a method for producing the probe for a scanning probe microscope. This method includes steps of: immersing a probe in a solution containing an electrochemically-polymerizable monomer; and applying a voltage to the probe so as to polymerize the monomer, thereby forming a cover layer.
Preferably, the monomer solution includes a catalyst molecule.
Preferably, the above method further includes steps of: immersing a probe having the cover layer in a solution or dispersion solution containing a catalyst molecule; and applying a voltage to the probe, thereby uptaking the catalyst molecule in the cover layer.
According to one aspect of the present invention, the present invention relates to a method for processing an intended molecule using a scanning probe microscope having a probe. This probe has a cover layer containing an electrically conductive polymer, and a catalyst molecule being uptaken in the cover layer. This method includes steps of: moving the probe closer to the intended molecule; and applying a voltage to the electrically conductive polymer so as to release the catalyst molecule to the intended molecule, thereby causing a chemical reaction.
The present invention also relates to a scanning probe microscope which includes: the above probe; means for controlling relative positions of the probe and the sample; and means for detecting an interaction between the probe and the sample.